title: Induction of a 55 kDa acetylcholinesterase protein during apoptosis and its negative regulation by the Akt pathway.
abstract: Acetylcholinesterase (AChE) is emerging as an important contributor to apoptosis in various cell types. However, overexpression of AChE does not initiate apoptosis, and cells which express AChE at basal levels grow normally, suggesting that AChE may function differently between normal and apoptotic conditions. In this study, we determined that an AChE-derived protein (∼55 kDa) positively correlated with cellular apoptotic levels. The 55 kDa AChE protein was not a result of a novel splice variant of the AChE primary transcript. Instead, it was determined to be a cleaved fragment of the full-length 68 kDa AChE protein that could not be inhibited by cycloheximide (CHX) but could be suppressed by caspase inhibitors in apoptotic PC-12 cells. Furthermore, activation of the Akt cascade abolished the 55 kDa protein, and both AChE protein forms (68 and 55 kDa) accumulated in the nucleus during apoptosis. In a mouse model for ischemia/reperfusion (I/R)-induced acute renal failure, the 55 kDa AChE protein was detected in the impaired organs but not in the normal ones, and its levels correlated with the genotype of the mice. In summary, a 55 kDa AChE protein resulting from the cleavage of 68 kDa AChE is induced during apoptosis, and it is negatively regulated by the Akt pathway. This study suggests that an alternative form of AChE may play a role in apoptosis.
authors.affiliation: Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xie
authors.forename: Hua
authors.initials: H
authors.lastname: Jiang
authors.forename: Yi-Han
authors.initials: YH
authors.lastname: Wan
authors.forename: Ai-Ying
authors.initials: AY
authors.lastname: Du
authors.forename: Kai-Jie
authors.initials: KJ
authors.lastname: Guo
authors.forename: Te
authors.initials: T
authors.lastname: Liu
authors.forename: Wei-Yuan
authors.initials: WY
authors.lastname: Ye
authors.forename: Xin
authors.initials: X
authors.lastname: Niu
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.forename: Xiao-Qin
authors.initials: XQ
authors.lastname: Dong
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Zhang
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D004195:Disease Models, Animal; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D051379:Mice; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D003513:Cycloheximide; D051057:Proto-Oncogene Proteins c-akt; D000110:Acetylcholinesterase